Prenatal Diagnosis of Placenta Accreta Spectrum Disorders: Deep Learning Radiomics of Pelvic MRI.

BACKGROUND: Diagnostic performance of placenta accreta spectrum (PAS) by prenatal MRI is unsatisfactory. Deep learning radiomics (DLR) has the potential to quantify the MRI features of PAS. PURPOSE: To explore whether DLR from MRI can be used to identify pregnancies with PAS. STUDY TYPE: Retrospective. POPULATION: 324 pregnant women (mean age, 33.3 years) suspected PAS (170 training and 72 validation from institution 1, 82 external validation from institution 2) with clinicopathologically proved PAS (206 PAS, 118 non-PAS). FIELD STRENGTH/SEQUENCE: 3-T, turbo spin-echo T2-weighted images. ASSESSMENT: The DLR features were extracted using the MedicalNet. An MRI-based DLR model incorporating DLR signature, clinical model (different clinical characteristics between PAS and non-PAS groups), and MRI morphologic model (radiologists' binary assessment for the PAS diagnosis) was developed. These models were constructed in the training dataset and then validated in the validation datasets. STATISTICAL TESTS: The Student t-test or Mann-Whitney U, χ2 or Fisher exact test, Kappa, dice similarity coefficient, intraclass correlation coefficients, least absolute shrinkage and selection operator logistic regression, multivariate logistic regression, receiver operating characteristic (ROC) curve, DeLong test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI), calibration curve with Hosmer-Lemeshow test, decision curve analysis (DCA). P < 0.05 indicated a significant difference. RESULTS: The MRI-based DLR model had a higher area under the curve than the clinical model in three datasets (0.880 vs. 0.741, 0.861 vs. 0.772, 0.852 vs. 0.675, respectively) or MRI morphologic model in training and independent validation datasets (0.880 vs. 0.760, 0.861, vs. 0.781, respectively). The NRI and IDI were 0.123 and 0.104, respectively. The Hosmer-Lemeshow test had nonsignificant statistics (P = 0.296 to 0.590). The DCA offered a net benefit at any threshold probability. DATA CONCLUSION: An MRI-based DLR model may show better performance in diagnosing PAS than a clinical or MRI morphologic model. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Algorithm as Recommending Source and Persuasive Health Communication: Effects of Source Cues, Language Intensity, and Perceived Issue Involvement.

Algorithms are now playing significant roles in online health information selection and recommendation. A question arises as to when and why people would be persuaded by the content they recommend. We conducted a 4 (recommending source: algorithm, other users, a friend, the CDC) x 2 (language intensity: high vs. low) experiment to find out. Participants (N = 299) were exposed to a health-related public service announcement embedded in a social media post. The results showed that overall, an algorithm induced a similar level of compliance intention compared with other recommending sources. We also found a significant three-way interaction when comparing the effects of the algorithm and the CDC: for individuals with low issue involvement, the algorithm was less persuasive when paired with a message with high language intensity. In contrast, for high-involvement individuals, the algorithm elicited more fear than the CDC when recommending an assertive message, partially leading to more compliance intention.

Comprehensive Analysis of the Function and Prognostic Value of TAS2Rs Family-Related Genes in Colon Cancer.

In the realm of colon carcinoma, significant genetic and epigenetic diversity is observed, underscoring the necessity for tailored prognostic features that can guide personalized therapeutic strategies. In this study, we explored the association between the type 2 bitter taste receptor (TAS2Rs) family-related genes and colon cancer using RNA-sequencing and clinical datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Our preliminary analysis identified seven TAS2Rs genes associated with survival using univariate Cox regression analysis, all of which were observed to be overexpressed in colon cancer. Subsequently, based on these seven TAS2Rs prognostic genes, two colon cancer molecular subtypes (Cluster A and Cluster B) were defined. These subtypes exhibited distinct prognostic and immune characteristics, with Cluster A characterized by low immune cell infiltration and less favorable outcomes, while Cluster B was associated with high immune cell infiltration and better prognosis. Finally, we developed a robust scoring system using a gradient boosting machine (GBM) approach, integrated with the gene-pairing method, to predict the prognosis of colon cancer patients. This machine learning model could improve our predictive accuracy for colon cancer outcomes, underscoring its value in the precision oncology framework.

Efficiency and safety of high-power ablation guided by Lesion size index: An ex vivo porcine heart study.

BACKGROUND: Although Lesion size index (LSI) has been reported to highly predict radiofrequency lesion size in vitro, its accuracy in lesion size and steam pop estimation has not been well investigated for every possible scenario. METHODS: Initially, radiofrequency ablations were performed on porcine myocardial slabs at various power, CF, and time settings with blinded LSI. Subsequently, radiofrequency power at 20, 30, 40, 50, and 60 W was applied at CF values of 5, 10, 20, and 30 g to reach target LSIs of 4, 5, 6, and 7. Lesion size and steam pops were recorded for each ablation. RESULTS: Lesion size was positively correlated with LSI regardless of power settings (p < 0.001). The linear correlation coefficients of lesion size and LSI decreased at higher power settings. At high power combined with high CF settings (50 W/20 g), lesion depth and LSI showed an irrelevant correlation (p = 0.7855). High-power ablation shortened ablation time and increased the effect of resistive heating. LSI could predict the risk of steam pops at high-power settings with the optimal threshold of 5.65 (sensitivity, 94.1%; specificity, 46.1%). The ablation depth of the heavy heart was shallower than that of the light heart under similar ablation settings. CONCLUSIONS: LSI could predict radiofrequency lesion size and steam pops at high power settings in vitro, while synchronous high power and high CF should be avoided. Lighter hearts require relatively lower ablation settings to create appropriate ablation depth.

Personalized Fair Split Learning for Resource-Constrained Internet of Things.

With the flourishing development of the Internet of Things (IoT), federated learning has garnered significant attention as a distributed learning method aimed at preserving the privacy of participant data. However, certain IoT devices, such as sensors, face challenges in effectively employing conventional federated learning approaches due to limited computational and storage resources, which hinder their ability to train complex local models. Additionally, in IoT environments, devices often face problems of data heterogeneity and uneven benefit distribution between them. To address these challenges, a personalized and fair split learning framework is proposed for resource-constrained clients. This framework first adopts a U-shaped structure, dividing the model to enable resource-constrained clients to offload subsets of the foundational model to a central server while retaining personalized model subsets locally to meet the specific personalized requirements of different clients. Furthermore, to ensure fair benefit distribution, a model-aggregation method with optimized aggregation weights is used. This method reasonably allocates model-aggregation weights based on the contributions of clients, thereby achieving collaborative fairness. Experimental results demonstrate that, in three distinct data heterogeneity scenarios, employing personalized training through this framework exhibits higher accuracy compared to existing baseline methods. Simultaneously, the framework ensures collaborative fairness, fostering a more balanced and sustainable cooperation among IoT devices.

ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury.

Cuproptosis resulting from copper (Cu) overload has not yet been investigated in diabetic cardiomyopathy (DCM). Advanced glycosylation end products (AGEs) induced by persistent hyperglycemia play an essential role in cardiotoxicity. To clarify whether cuproptosis was involved in AGEs-induced cardiotoxicity, we analyzed the toxicity of AGEs and copper in AC16 cardiomyocytes and in STZ-induced or db/db-diabetic mouse models. The results showed that copper ionophore elesclomol induced cuproptosis in cardiomyocytes. It was only rescued by copper chelator tetrathiomolybdate rather than by other cell death inhibitors. Intriguingly, AGEs triggered cardiomyocyte death and aggravated it when incubated with CuCl2 or elesclomol-CuCl2. Moreover, AGEs increased intracellular copper accumulation and exhibited features of cuproptosis, including loss of Fe-S cluster proteins (FDX1, LIAS, NDUFS8 and ACO2) and decreased lipoylation of DLAT and DLST. These effects were accompanied by decreased mitochondrial oxidative respiration, including downregulated mitochondrial respiratory chain complex, decreased ATP production and suppressed mitochondrial complex I and III activity. Additionally, AGEs promoted the upregulation of copper importer SLC31A1. We predicted that ATF3 and/or SPI1 might be transcriptional factors of SLC31A1 by online databases and validated that by ATF3/SPI1 overexpression. In diabetic mice, copper and AGEs increases in the blood and heart were observed and accompanied by cardiac dysfunction. The protein and mRNA profile changes in diabetic hearts were consistent with cuproptosis. Our findings showed, for the first time, that excessive AGEs and copper in diabetes upregulated ATF3/SPI1/SLC31A1 signaling, thereby disturbing copper homeostasis and promoting cuproptosis. Collectively, the novel mechanism might be an alternative potential therapeutic target for DCM.

Cirsiliol regulates mitophagy in colon cancer cells via STAT3 signaling.

BACKGROUND: Mitophagy is a type of selective autophagy for dysfunctional mitochondria and plays a key role in tumorigenesis and cancer progression. However, whether mitophagy plays a role in colon cancer remains unclear. Cirsiliol is a natural product and has been found to exert anti-cancer effects in multiple tumors. The effects of cirsiliol in the tumorigenesis and progression of colon cancer remain unknown. METHODS: CCK8 assay, plate cloning assay, and cell scratch assay were performed to determine cell viability, colony formation, and wound healing abilities of HCT116 and SW480 cells. JC-1 staining, H2DCFDA staining, and Mito-Tracker Red staining were carried out to evaluate mitochondrial membrane potential (Δψm), intracellular reactive oxygen species (ROS) level, and mitochondrial morphology. Molecular docking technology was utilized to predict interaction of cirsiliol and signal transducer and activator of transcription 3 (STAT3). Immunofluorescence staining was used to measure nuclear translocation of STAT3. The protein levels of phosphorylated STAT3 (Y705), total STAT3, and mitophagy proteins were detected by western blot. RESULTS: In this study, we first found that cirsiliol inhibited cell viability, colony formation, and wound healing abilities of HCT116 and SW480 colon cancer cells. Moreover, cirsiliol suppressed Δψm, increased ROS production, and disrupted mitochondrial morphology via inhibiting the levels of mitophagy proteins including PINK1, Parkin, BNIP3, and FUNDC1. Application of mitophagy activator improved the levels of mitophagy-related proteins, and ameliorated Δψm and ROS levels. According to the result of molecular docking, we found that cirsiliol potentially bound to the SH2 domain of STAT3, the key domain for the functional activation of STAT3. Moreover, it was found that cirsiliol inhibited constitutive and IL­6­induced STAT3 phosphorylation and nuclear translocation by western blot and immunofluorescence analysis. Comparing with cirsiliol group, we found that overexpression of STAT3 restored the expressions of mitophagy proteins. CONCLUSIONS: Cirsiliol targets STAT3 to inhibit colon cancer cell proliferation by regulating mitophagy.

MRI-radiomics-clinical-based nomogram for prenatal prediction of the placenta accreta spectrum disorders.

OBJECTIVES: To investigate whether an MRI-radiomics-clinical-based nomogram can be used to prenatal predict the placenta accreta spectrum (PAS) disorders. METHODS: The pelvic MR images and clinical data of 156 pregnant women with pathologic-proved PAS (PAS group) and 115 pregnant women with no PAS (non-PAS group) identified by clinical and prenatal ultrasonic examination were retrospectively collected from two centers. These pregnancies were divided into a training (n = 133), an independent validation (n = 57), and an external validation (n = 81) cohort. Radiomic features were extracted from images of transverse oblique T2-weighted imaging. A radiomics signature was constructed. A nomogram, composed of MRI morphological findings, radiomic features, and prenatal clinical characteristics, was developed. The discrimination and calibration of the nomogram were conducted to assess its performance. RESULTS: A radiomics signature, including three PAS-related features, was associated with the presence of PAS in the three cohorts (p < 0.001 to p = 0.001). An MRI-radiomics-clinical nomogram incorporating radiomics signature, two prenatal clinical features, and two MRI morphological findings was developed, yielding a higher area under the curve (AUC) than that of the MRI morphological-determined PAS in the training cohort (0.89 vs. 0.78; p < 0.001) and external validation cohort (0.87 vs. 0.75; p = 0.003), while a comparable AUC value in the validation cohort (0.91 vs. 0.81; p = 0.09). The calibration was good. CONCLUSIONS: An MRI-radiomics-clinical nomogram had a robust performance in antenatal predicting the PAS in pregnancies. KEY POINTS: • An MRI-radiomics-clinical-based nomogram might serve as an adjunctive approach for the treatment decision-making in pregnancies suspicious of PAS. • The radiomic score provides a mathematical formula that predicts the possibility of PAS by using the MRI data, and pregnant women with PAS had higher radiomic scores than those without PAS.

To Explore the Effect of Preoperative Hemodynamic Factors on The Outcome of Pseudolumen After Stanford Type B Aortic Dissection TEVAR Based on Computer Fluid Dynamics.

OBJECTIVE: The preoperative aortic hemodynamic data of patients with Stanford type B aortic dissection were obtained by computer fluid dynamics (CFD). Then we explored the relationship between hemodynamic data and short-term residual pseudolumen after thoracic endovascular aortic repair (TEVAR) and predict the latter through the former. METHODS: We collected the relevant data of 53 patients who underwent TEVAR in our hospital. They were divided into the A group (residual false lumen group) and B group (closed false lumen group), according to whether there was a residual false cavity around the stent recently after TEVAR. Three-dimensional reconstruction and CFD analysis of the thoracic and abdominal aorta was performed by DSCTA before the operation to obtain the aortic wall shear stress (WSS) and maximum blood flow velocity of the true and false lumen at the entrance, middle point of the long axis, and distal decompression port at the peak time of ventricular systolic velocity. Through the statistical analysis, we further studied the predictive value of hemodynamic data for residual pseudolumen. RESULTS: There was no significant difference in age, male, preoperative and postoperative thoracic and abdominal aorta DSCTA interval, history of hypertension, history of diabetes, smoking, Pt and APTT at admission between the two groups (P > 0.05). The blood flow velocity and shear stress at the entrance of the false lumen and the distal decompression port in the two groups were statistically significant (P < 0.05), while the other hemodynamic indexes were not statistically significant (P > 0.05). Binary logistic regression analysis further showed that the shear stress of the false lumen at the level of the distal decompression port (OR = 1.73, P = 0.01) was an independent risk factor for the residual false lumen around the stent in the early stage after TEVAR. The ROC curve analysis showed that the AUC area of the ROC curve corresponding to the shear stress of the false cavity at the level of the distal decompression port was 0.83, the best cross-sectional value was 9.49pa, and the sensitivity and specificity were 84.60% and 72.50%. CONCLUSIONS: The residual pseudolumen after TEVAR is related to the hemodynamic factors in the aorta before TEVAR. Preoperative hemodynamic data also have good predictive value. When the shear stress of the false lumen at the level of the distal decompression port is greater than 9.49pa, the probability of residual false lumen around the stent during the perioperative period significantly increases.

Melatonin ameliorates oxidative stress-mediated injuries through induction of HO-1 and restores autophagic flux in dry eye.

This study aimed to investigate the protective effect of melatonin on the corneal epithelium in dry eye disease(DED) and explore its underlying mechanism. Human corneal epithelial(HCE) cells was exposure to t-butylhydroperoxide(tBH), C57BL/6 mice were injected of subcutaneous scopolamine to imitate DED. Melatonin was used both in vivo and in vitro. Cell viability was detected by Cell Counting Kit-8 assay and Lactate Dehydrogenase Leakage. The change of cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and apoptosis was analyzed by flow cytometry. Western blot assays and immunofluorescence were carried out to measure protein changes. mRNA expression was investigated by RNA sequencing (RNA-Seq) and quantitative real-time PCR. The change of autophagic flux were observed through mCherry-GFP-LC3 transfection and electron microscopy(TEM). Clinical parameters of corneal epithelium defects, conjunctival goblet cells, tear volume, and level of ocular surface inflammation was recorded. Melatonin was able to reduce excessive ROS production and maintain mitochondrial function. TEM assay found melatonin rescued impaired autophagic flux under tBH. Moreover, melatonin significantly preserved cell viability, abolished LDH release, and decreased apoptosis. RNA-Seq indicated that melatonin greatly activating hemeoxygenase-1 (HO-1) expression. Interestingly, HO-1 ablation largely attenuated its protective effects. Besides, in dry eye mouse model, intraperitoneal injection of melatonin showed greatly improved clinical parameters, inhibited activated NLRP3 inflammation cascade, and increased density of goblet cells and tear volume. Thus, melatonin protects corneal epithelial cells from oxidative damage, maintain normal level of autophagy, and reduce inflammation via trigging HO-1 expression in DED.

Conjunctival microvascular responses to anti-inflammatory treatment in patients with dry eye.

PURPOSE: This study characterized conjunctival microvascular morphological and haemodynamic responses after anti-inflammatory treatment in dry eye (DE). MATERIALS AND METHODS: Twenty-five patients with moderate DE (17 females and 8 males aged 48 ± 16 years) who underwent anti-inflammatory therapy (0.1% fluorometholone) and 25 healthy subjects (20 females and 5 males aged 48 ± 17 years) recruited as controls were enrolled. The conjunctival blood flow rate (BFR), blood flow velocity (BFV) and vessel diameter were measured by functional slit-lamp biomicroscopy (FSLB). DE symptoms and signs were assessed. All measurements were performed at baseline and at 30 and 60 days after commencement of treatment. RESULTS: At baseline, the conjunctival BFR, BFV, and vessel diameter were higher in the DE group than in the control group (p < 0.05). The BFR, BFV and corneal fluorescein staining (CFS) scores decreased at 60 days after therapy compared to at baseline and 30 days (all pcorrected < 0.05); Ocular surface diseases index (OSDI), the hyperaemia index (HI) and vessel diameters only showed significant decreases at 30 days. Moreover, significant increases in the noninvasive tear film break-up time (NI-BUT) and Schirmer I test score (ST) were observed. The CFS score correlated positively with BFV (r = 0.46), BFR (r = 0.58) and vessel diameter (r = 0.47). CONCLUSION: This study characterized conjunctival microvascular responses to anti-inflammatory treatment in DE patients. The results suggest that conjunctival BFV and BFR can be used as dynamic markers for treatment efficacy in DE.

Healing characteristics of acellular porcine corneal stroma following therapeutic keratoplasty.

BACKGROUND: Acellular porcine corneal stroma (APCS) has proven to be a promising alternative to traditional corneal grafts. This prospective case series was conducted to further investigate the healing characteristics of APCS following keratoplasty. METHODS: Twenty-seven patients undergoing APCS implantation to treat infectious keratitis were included. The patients were followed up for 12 months after surgery. The main outcome measures included visual acuity, corneal transparency, graft thickness, and cellular and nerve regeneration. RESULTS: In the operated eyes, the best-corrected visual acuity (BCVA, in logarithm of the minimal angle of resolution [logMAR] units) increased from 1.23 ± 0.95 logMAR before surgery to 0.23 ± 0.18 logMAR at 12 months after surgery (P < .001). The contrast sensitivity was still evidently reduced, especially at higher spatial frequencies. Gradual transparency improvement was observed in APCS grafts post-operatively. After implantation, the APCS graft thickness initially increased (day 1 = 592.41 ± 52.69 µm) but then continuously decreased until 3 months after surgery (1 month = 449.26 ± 50.38 µm; 3 months = 359.63 ± 34.14 µm, P < .001). Graft reepithelialization was completed within 1 week. In the in vivo confocal microscopy scans, host keratocytes began to repopulate the APCS grafts between 3 and 6 months post-operatively; subbasal nerve regeneration was only noted in 18.52% (5/27) of the eyes by 12 months after surgery. CONCLUSIONS: Acellular porcine corneal stroma functions as an effective alternative to human corneal tissue in lamellar keratoplasty. However, APCS is somewhat different from fresh human cornea in term of the post-operative healing process, which warrants the attention of both clinicians and patients.

Risk factors influencing survival of acellular porcine corneal stroma in infectious keratitis: a prospective clinical study.

BACKGROUND: A worldwide lack of donor corneas demands the bioengineered corneas be developed as an alternative. The primary objective of the current study was to evaluate the efficacy of acellular porcine corneal stroma (APCS) transplantation in various types of infectious keratitis and identify risk factors that may increase APCS graft failure. METHODS: In this prospective interventional study, 39 patients with progressive infectious keratitis underwent therapeutic lamellar keratoplasty using APCS and were followed up for 12 months. Data collected for analysis included preoperative characteristics, visual acuity, graft survival and complications. Graft survival was evaluated by the Kaplan-Meier method and compared with the log-rank test. RESULTS: The percentage of eyes that had a visual acuity of 20/40 or better increased from 10.3% preoperatively to 51.2% at 12 months postoperatively. Twelve patients (30.8%) experienced graft failure within the follow-up period. The primary reasons given for graft failure was noninfectious graft melting (n = 5), and the other causes included recurrence of primary infection (n = 4) and extensive graft neovascularization (n = 3). No graft rejection was observed during the follow-up period. A higher relative risk (RR) of graft failure was associated with herpetic keratitis (RR = 8.0, P = 0.046) and graft size larger than 8 mm (RR = 6.5, P < 0.001). CONCLUSIONS: APCS transplantation is an alternative treatment option for eyes with medically unresponsive infectious keratitis. Despite the efficacy of therapeutic lamellar keratoplasty with APCS, to achieve a good prognosis, restriction of surgical indications, careful selection of patients and postoperative management must be emphasized. Trial registration Prospective Study of Deep Anterior Lamellar Keratoplasty Using Acellular Porcine Cornea, NCT03105466. Registered 31 August 2016, ClinicalTrails.gov.

Tacrolimus interacts with voriconazole to reduce the severity of fungal keratitis by suppressing IFN-related inflammatory responses and concomitant FK506 and voriconazole treatment suppresses fungal keratitis.

Purpose: To investigate the expression and roles of type I and II interferons (IFNs) in fungal keratitis, as well as the therapeutic effects of tacrolimus (FK506) and voriconazole on this condition. Methods: The mRNA and protein expression levels of type I (IFN-α/ß) and II (IFN-γ) IFNs, as well as of related downstream inflammatory cytokines (interleukin (IL)-1α, IL-6, IL-12, and IL-17), were detected in macrophages, neutrophils, lymphocytes, and corneal epithelial cells (A6(1) cells) stimulated with zymosan (10 mg/ml) for 8 or 24 h. A fungal keratitis mouse model was generated through intrastromal injection of Aspergillus fumigatus, and the mice were then divided into four groups: group I, the PBS group; group II, the voriconazole group; group III, the FK506 group; and group IV, the voriconazole plus 0.05% FK506 group. Corneal damage was evaluated with clinical scoring and histological examination. In addition, the mRNA and protein expression levels of type I (IFN-α/ß) and type II (IFN-γ) IFNs, as well as related inflammatory cytokines, were determined at different time points using quantitative real-time PCR (qRT-PCR) and western blotting. Results: After zymosan stimulation of mouse neutrophils, lymphocytes, macrophages, and A6(1) cells, the IFN mRNA and protein expression levels were markedly increased until 24 h, peaking at 8 h (p<0.001). The mRNA and protein expression levels of inflammatory cytokines (IL-1α, IL-6, IL-12, and IL-17) were also upregulated after zymosan stimulation. Moreover, type I (IFN-α/ß) and type II (IFN-γ) IFN expression levels were increased and positively correlated with the progression of fungal keratitis in vivo. FK506 administered with voriconazole reduced the pathological infiltration of inflammatory cells into the cornea and downregulated the expression levels of IFNs and related inflammatory cytokines. Conclusions: In conclusion, this study demonstrated that type I and II IFN levels were markedly increased in fungal keratitis and that FK506 combined with voriconazole decreased the severity of fungal keratitis by suppressing type I and II IFNs and their related inflammatory responses.

Microvascular abnormalities in dry eye patients.

This study was conducted to evaluate conjunctival blood flow velocities and microvascular network density in patients with dry eye disease (DED). Twenty-five patients with DED and 25 healthy controls were recruited. The microvasculature and microcirculation of the temporal bulbar conjunctiva of the right eyes were assessed using a functional slit-lamp biomicroscope. Vascular variables included blood flow velocity (BFV), blood flow rate (BFR), microvascular network density and vessel diameter. A fractal analysis was performed using the box counting method to measure the fractal dimension (Dbox) representing the vessel density. The bulbar BFV was 0.59 ±â€¯0.09 mm/s in the DED group and 0.47 ±â€¯0.12 in the control group (P < 0.001). BFR was 169.5 ±â€¯1.8 in the DED group compared to the control group (107.2 ±â€¯49.6) (P < 0.001). Dbox was higher in DED patients (1.65 ±â€¯0.04) than controls (1.60 ±â€¯0.07, P < 0.05). Moreover, the vessel diameter was larger in the DED group (21.8 ±â€¯1.8 µm) compared with controls (17.9 ±â€¯2.2 µm, P < 0.001). Dbox was positively related with ocular surface disease index (OSDI) in patients with DED (r = 0.54, P = 0.008). Microvascular alterations were found in the bulbar conjunctiva of DED patients, including increased blood flow velocity, higher vessel density and larger vessel diameter.

Genetic association analyses of fast plasma glucose level in pre-menopausal Chinese women: potential interaction between osteocalcin and oestrogen receptor α.

BACKGROUND: Fasting plasma glucose (FPG) levels are usually tightly regulated within a narrow physiologic range. Variation of FPG levels is clinically important and is strongly heritable. Several lines of evidence suggest the importance of the oestrogen receptor α (ER-α) and osteocalcin (also known as BGP, for bone Gla protein) in determining FPG; however, whether their polymorphisms are associated with FPG variation is not well understood. AIM: To investigate whether ER-a PvuII and BGP HindIII genetic polymorphisms and their potential interaction are associated with FPG variation. SUBJECTS AND METHODS: The study subjects were 328 unrelated pre-menopausal Chinese women aged 21 years and over (mean age ± SD, 33.2 ± 5.9 years), with an average FPG of 4.92 (SD = 0.81). All subjects were genotyped at the ER-α PvuII and BGP HindIII loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). RESULTS: The ER-α PvuII genotypes were significantly associated with FPG (p = 0.007). In addition, a significant interaction was observed of the ER-α PvuII polymorphism with BGP HindIII polymorphism on FPG variation (p = 0.013), although the BGP HindIII polymorphism was not shown to be individually associated with FPG. CONCLUSION: The PvuII polymorphism of the ER-α gene and its potential interaction with the HindIII polymorphism of the BGP gene were associated with FPG in pre-menopausal Chinese women.

Biased Dopamine D2 Receptors Exhibit Distinct Intracellular Trafficking Properties and ERK Activation in Different Subcellular Domains.

Biased signaling or functional selectivity refers to the ability of an agonist or receptor to selectively activate a subset of transducers such as G protein and arrestin in the case of G protein-coupled receptors (GPCRs). Although signaling through arrestin has been reported from various GPCRs, only a few studies have examined side-by-side how it differs from signaling via G protein. In this study, two signaling pathways were compared using dopamine D2 receptor (D2R) mutants engineered via the evolutionary tracer method to selectively transduce signals through G protein or arrestin (D2G and D2Arr, respectively). D2G mediated the inhibition of cAMP production and ERK activation in the cytoplasm. D2Arr, in contrast, mediated receptor endocytosis accompanied by arrestin ubiquitination and ERK activation in the nucleus as well as in the cytoplasm. D2Arr-mediated ERK activation occurred in a manner dependent on arrestin3 but not arrestin2, accompanied by the nuclear translocation of arrestin3 via importin1. D2R-mediated ERK activation, which occurred in both the cytosol and nucleus, was limited to the cytosol when cellular arrestin3 was depleted. This finding supports the results obtained with D2Arr and D2G. Taken together, these observations indicate that biased signal transduction pathways activate distinct downstream mechanisms and that the subcellular regions in which they occur could be different when the same effectors are involved. These findings broaden our understanding on the relation between biased receptors and the corresponding downstream signaling, which is critical for elucidating the functional roles of biased pathways.

Transcriptome Analysis of Salvia miltiorrhiza under Drought Stress.

Phenolic acids are one of the major secondary metabolites accumulated in Salvia miltiorrhiza with various pharmacological activities. Moderate drought stress can promote the accumulation of phenolic acids in S. miltiorrhiza, while the mechanism remains unclear. Therefore, we performed transcriptome sequencing of S. miltiorrhiza under drought treatment. A total of 47,169 unigenes were successfully annotated in at least one of the six major databases. Key enzyme genes involved in the phenolic acid biosynthetic pathway, including SmPAL, SmC4H, Sm4CL, SmTAT, SmHPPR, SmRAS and SmCYP98A14, were induced. Unigenes annotated as laccase correlated with SmRAS and SmCYP98A14 were analyzed, and seven candidates that may be involved in the key step of SalB biosynthesis by RA were obtained. A total of 15 transcription factors significantly up-regulated at 2 h and 4 h potentially regulating phenolic acid biosynthesis were screened out. TRINITY_DN14213_c0_g1 (AP2/ERF) significantly transactivated the expression of SmC4H and SmRAS, suggesting its role in the regulation of phenolic acid biosynthesis. GO and KEGG enrichment analysis of differential expression genes showed that phenylpropanoid biosynthesis and plant hormone signal transduction were significantly higher. The ABA-dependent pathway is essential for resistance to drought and phenolic acid accumulation. Expression patterns in drought and ABA databases showed that four PYLs respond to both drought and ABA, and three potential SnRK2 family members were annotated and analyzed. The present study presented a comprehensive transcriptome analysis of S. miltiorrhiza affected by drought, which provides a rich source for understanding the molecular mechanism facing abiotic stress in S. miltiorrhiza.

Exposure to anti-Black Lives Matter movement and obesity of the Black population.

RATIONALE: Black Lives Matter (BLM) is a social movement against systematic injustice and police violence toward Black people whose goal is to ensure their safety and the expression of their culture. As BLM gained momentum, counter-movements emerged, such as All Lives Matter (ALM), White Lives Matter (WLM), and Blue Lives Matter (BlueLM). Because they undermine support for Black people's safety and culture, exposure to stances against BLM can be a race-related stressor. Although the perception of racial discrimination has been associated with negative health outcomes in Black people, it is not clear whether exposure to negative stances on a race-related social issue is associated with worse health outcomes. OBJECTIVE: We investigated whether living in areas of the United States with a high prevalence of negative stances on BLM is associated with worse health outcomes, such as higher body mass index (BMI) and prevalence of obesity. METHODS: We scraped geo-coded tweets (N = 51,020) that contained #BLM, #ALM, #WLM, and #BlueLM from 2014 to 2016. We determined the stances of the tweets on BLM using machine learning algorithms and aggregated stances at the metropolitan or micropolitan statistical area (MMSA) levels. Participants' BMI and obesity status were derived from the 2017 BRFSS SMART data in 76 MMSAs, as compiled by the Centers for Disease Control and Prevention (N = 20,530). RESULTS: After controlling for individual- and regional-level covariates, regional measures of racism and police brutality rate, and baseline BMI in 2014 aggregated on MMSA level, Black people had a higher BMI and prevalence of obesity in areas that showed higher negative stances on BLM. Stances against BLM were positively associated with implicit racism against Black people and can be an acute race-related stressor associated with negative downstream health outcomes. CONCLUSION: Negative societal sentiments around race-related issues may be detrimental to the health outcomes of minority populations.

Myeloid-derived suppressor cells ameliorate corneal alkali burn through IL-10-dependent anti-inflammatory properties.

This study aims to investigate the efficiency and the underlying mechanism of myeloid-derived suppressor cells (MDSCs) in corneal alkali burns (CAB). In the study, CD11b+ Gr-1+ cells from C57BL/6J mice bone marrow were cultured and induced. Cell activity and immunoregulatory function were assessed by flow cytometry in vitro. The optimal strategy of MDSCs therapy was assessed by slit-lamp microscopy, and flow cytometry in vivo. The therapeutic effects of MDSCs and the critical signaling pathway were investigated by hematoxylin-eosin (HE) staining, slit-lamp microscopy, flow cytometry, and immunofluorescence. The expression level of the NLRP3 inflammasome pathway was examined. The crucial biochemical parameters of MDSCs were examined by RNA-seq and qPCR to screen out the key regulators. The mechanism of MDSCs' therapeutic effects was explored using MDSCs with IL-10 knockout/rescue by slit-lamp microscopy, HE staining, and qPCR evaluation. The cell frequencies of macrophages and neutrophils in the cornea were examined by flow cytometry in vivo. The results demonstrated that the induced MDSCs meet the standard of phenotypic and functional characteristics. The treatment of 5 × 105 MDSCs conjunctival injection on alternate days significantly ameliorated the disease development, downregulated the NLRP3 inflammasome pathway, and decreased the cell frequencies of macrophages and neutrophils in vivo significantly. IL-10 was screened out to be the critical factor for MDSCs therapy. The therapeutic effects of MDSCs were impaired largely by IL-10 knock-out and saved by the IL-10 supplement. In conclusion, MDSCs therapy is a promising therapeutic solution for CAB. MDSCs fulfilled immunoregulatory roles for CAB by IL-10-dependent anti-inflammatory properties.